The primary goals of our studies are to describe the effects of hypoxic, anemic and carbon monoxide hypoxia on cerebral blood flow and O2 consumption in unanesthetized fetal, newborn and adult sheep. Cerebral blood flow is measured with the radioactive microsphere technique. Cerebral O2 consumption is calculated as the product of cerebral blood flow and the difference in O2 content between carotid and sagittal sinus blood; cerebral blood flow per unit O2 consumption, by a rearrangement of the Fick equation, is determined by the cerebral arteriovenous difference of O2 content. Work just completed has demonstrated that in the lamb cerebral blood flow during hypoxic hypoxia responds to the O2 content rather than the PO2 of arterial blood. We will extend these studies by examining the effects of changes in arterial O2 content in the absence of changes in PaO2 during isovolemic anemia in fetal and newborn lambs. During hypoxic hypoxia the increase in cerebral blood flow minimizes changes in cerebral O2 delivery. We will determine whether this also applies during anemic hypoxia. Secondly, we intend to determine the effects of shifts in the oxyhemoglobin dissociation curve on cerebral blood flow and O2 consumption in the lamb. Studies in lambs showed that CO hypoxia resulted in a larger cerebral blood flow at the same arterial O2 content than hypoxic hypoxia. It is conceivable that this was due to the shift in the O2 dissociation curve that accompanies CO hypoxia. We will therefore shift the dissociation curve by exchange transfusing the lamb with adult blood, which has a P50 approximately 20mmHg greater than fetal blood. Thirdly, we intend to compare the cerebrovascular responses of the lamb to CO hypoxia and to changes in arterial PCO2 with those in the adult.